Scientists suspect infectious disease shaped human origins

Roughly 100,000 years ago, human evolution hit a bottleneck: Our ancestors had been reduced to perhaps 5,000-10,000 individuals living in Africa. In time, modern humans would emerge from this population eventually replacing all other evolutionary cousins, such as the Neanderthals.

The cause of the bottleneck remains a mystery, with theories ranging from cultural developments like language to climate-altering events, among them a massive volcanic eruption.

Add another possible factor: infectious disease.

Using genome sequencing, an international team, led by scientists at the UC San Diego School of Medicine, discovered two inactive genes as part of a larger family of immune system genes believed to have been very active in human evolution. This suggests that when the genes in question became inactive, it gave ancestors of modern humans an upper hand by eliminating a protein target favored by bacteria particularly lethal to newborns and infants.

Such pinpoint mutations in a small, restricted population would have had an enormous positive effect on species survival allowing descendents to expand dramatically in both number and range.

The findings appear in The Proceedings of the National Academy of Sciences. News release at

The study focused on HLA (human leukocyte antigen), a gene that helps the body’s immune system identify cells infected by viruses and bacteria. Individuals possess many different variations of HLA and many drug hypersensitivity reactions are HLA-linked. Unfortunately, HLA-linked hypersensitivity often doesn’t surface during clinical trials, but only after a drug is approved and taken by thousands of people.

The LIAI team found that certain drugs can alter which peptides (pieces of proteins) specific HLA molecules “show” to the immune system creating a case of mistaken identity in which these peptides, otherwise never be seen by the immune system, initiate drug hypersensitivity. The team has developed tests to identify drug compounds at risk of setting off such genetic-linked reactions.

Findings appear in the Proceedings of the National Academy of Sciences. News release at

Millions of pre-diabetic Americans may be at increased risk of stroke, but the precise degree of that threat is confounded by differing medical definitions.

An international team that included UCSD School of Medicine researchers reviewed 15 studies that looked at the association between pre-diabetes and stroke risk. The studies, published between 2004 and 2011, involved 760,925 participants.

Pre-diabetes occurs when blood glucose levels are consistently higher than normal, but not yet high enough to be diagnosed as diabetes. People with pre-diabetes typically have the same risk factors for cardiovascular disease as people with type 2 diabetes – high blood pressure, high cholesterol levels, and obesity – but the condition’s effect on future stroke risk has not been established.

Researchers found that an association between future stroke risks depended upon the definition of pre-diabetes as determined by a fasting glucose test. However, that clinical measure has been changed in the last 15 years. Therefore, applying the 1997 standard identified pre-diabetes in the studies as having a 21 percent chance of suffering a future stroke; applying a less stringent 2003 definition indicated no increased stroke risk.

Additional research is needed to determine the best definition predicting stroke risk among diabetics that includes an assessment of more recent glycemic biomarkers, followed by clinical trials involving drugs and/or lifestyle modification to evaluate the effect of treatments on reducing the risk of future strokes.